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Drugs and Fetal Development: Proceedings of an International Symposium on The Effect of Prolonged Drug Usage on Fetal Development held at Beit-Berl. Kfar Saba, Israel. September 14–17. 1971 PDF

551 Pages·1972·13.2 MB·English
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Preview Drugs and Fetal Development: Proceedings of an International Symposium on The Effect of Prolonged Drug Usage on Fetal Development held at Beit-Berl. Kfar Saba, Israel. September 14–17. 1971

DRUGS AND FETAL DEVELOPMENT ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: Nathan Back Chairman, Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo, New York N. R. Di Luzio Chairman, Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana Alfred Gellhorn University of Pennsylvania Medical School, Philadelphia, Pennsylvania Bernard Halpern College de France, Director of the Institute of Immuno.Biology, Paris, France Ephraim Katchalski Department of Biophysics, The Weizmann Institute of Science, Rehovoth, Israel David Kritchevsky Wistar Institute, Philadelphia, Pennsylvania Abel Lajtha New York State Research Institute for Neurochemistry and Drug Addiction, Ward's Island, New York Rodolfo Paoletti Institute of Pharmacology, University of Milan, Milan, Italy Volume 1 THE RETICULOENDOTHELIAL SYSTEM AND ATHEROSCLEROSIS Edited by N. R. Di Luzio and R. Paoletti· 1967 Volume 2 PHARMACOLOGY OF HORMONAL POLYPEPTIDES AND PROTEINS Edited by N. Back, L. Martini, and R. Paoletti' 1968 Volume 3 GERM·FREE BIOLOGY: Experimental and Clinical Aspects Edited by E. A. Mirand and N. Back' 1969 Volume 4 DRUGS AFFECTING LIPID METABOLISM Edited by W. L. Holmes, L. A. Carlson, and R. Paoletti' 1969 Volume 5 LYMPHATIC TISSUE AND GERMINAL CENTERS IN IMMUNE RESPONSE Edited by L. Fiore·Donati and M. G. Hanna, Jr.' 1969 Volume 6 RED CELL METABOLISM AND FUNCTION Edited by George J. Brewer' 1970 Volume 7 SURFACE CHEMISTRY OF BIOLOGICAL SYSTEMS Edited by Martin Blank' 1970 Volume 8 BRADYKININ AND RELATED KININS: Cardiovascular, Biochemical, and Neural Actions Edited by F. Sicuteri, M. Rocha e Silva, and N. Back' 1970 Volume 9 SHOCK: Biochemical, Pharmacological, and Clinical Aspects Edited by A. Bertelli and N. Back' 1970 Volume 10 THE HUMAN TESTIS Edited by E. Rosemberg and C. A. Paulsen' 1970 Volume 11 MUSCLE METABOLISM DURING EXERCISE Edited by B. Pernow and B. Saltin • 1971 Volume 12 MORPHOLOGICAL AND FUNCTIONAL ASPECTS OF IMMUNITY Edited by K. Lindahl.Kiessling, G. Aim, and M. G. Hanna, Jr. • 1971 Yolume 13 CHEMISTRY AND BRAIN DEYELOPMENT Edited by R. Paoletti and A. N. Davison· 1971 Yolume 14 MEMBRANE·BOUND ENZYMES Edited by G. Porcellati and F. di Jeso • 1971 Yolume 15 THE RETICULOENDOTHELIAL SYSTEM AND IMMUNE PHENOMENA Edited by N. R. Di Luzio and K. Flemming· 1971 Yolume 16A THE ARTERY AND THE PROCESS OF ARTERIOSCLEROSIS: Pathogenesis Edited by Stewart Wolf· 1971 Yolume 16B THE ARTERY AND THE PROCESS OF ARTERIOSCLEROSIS: Measurement and Modifiration Edited by Stewart Wolf· 1972 Yolume 17 CONTROL OF RENIN SECRETION Edited by Tatiana A. Assaykeen ·1972 Yolume 18 THE DYNAMICS OF MERISTEM CELL POPULATIONS Edited hy Morton W. Milll'r and Charles r.. Kuehnert. 1972 Yolume 19 SPHINGOLIPIDS, SPIIINGOLIPIDOSES AND ALLIED DISORDERS Edited by Bruno W. Yolk and Stanley M. Aronson • 1972 Volume 20 DRUG ABUSE: Nonmedical Use of Dependence.Producing DruJ!;s Edited by Simon Btesh • 1972 Yolume 21 V ASOI'EI'TI)) ES: C1l1'llIi,try. I'harma('()I()~y. and I'athophy,iolop:y Edited hy N. B(\(·k and F. Si(,lIt<"ri • 1'172 Volume 22 COMPARATIVE PATHOPHYSIOLOGY OF CIRCULATORY DISTURBANCES Edited by Colin M. Bloor. 1972 Volume 23 THE FUNDAMENTAL MECHANISMS OF SHOCK Edited by Lerner B. Hinshaw and Barbara G. Cox. 1972 Volume 24 THE VISUAL SYSTEM: Ncurophysiolo!(y, Biophysirs, and Their Cliniral Appli"ations Edited by G. B. Arden. 1972 Volume 25 GLYCOLIPIDS, GLYCOPROTEINS, AND MUCOPOLYSACCHARIDES OF THE NERVOUS SYSTEM Edited hy Vittorio Zambotti, Guido Tettamanti, and Maria!\razia Arrigoni • 1972 Volume 26 PHARMACOLOGICAL CONTROL OF LIPID METABOLISM Edited by William L. Holmes, Rodolfo Paoletti, and David Kritchevsky • 1972 Volume 27 DRUGS AND FETAL DEVELOPMENT Edited by Marcus A. KlinJ(berJ(, Armand Abramovici, and Juan Chemke· 1972 Volume 28 HEMOGLOBIN AND RED CELL STRUCTURE AND FUNCTION Edited hy George J. Brewer. 1972 DRUGS AND FETAL DEVELOPMENT Proceedin~s of an International Symposium on The Effect of Prolonged Drug Usa~e on Fetal Development held at Beit-Berl. I(far Saba, Israel. September 14-17, 1971 Edited by Marcus A. Klingberg Head, Department of Epidemiology and Deputy Scientific Director Israel Institute for Biological Research and Tel.Aviv University Medical School Ness·Ziona, Israel Armand Abramovici Director, Laboratory of Developmental Pathology J. Casper Department of Pathology, Beilinson Hospital and Tel·Aviv University Medical School Petah·Tikva, Israel and Juan Chemke Director, Birth Defects Clinic Departments of Pediatrics A and Pediatric Research Kaplan Hospital (affiliated with the Hebrew University and Hadassah :\Iedil'al School, Jerusalem) Rehovot, Israel The Symposium on The Effect of Prolonged Drug Usage on Fetal Development was held under the auspices of Israel Academy of Sciences and Humanities Tel-Aviv University Medical School Israel Institute for Biological Research Israel Society for Congenital Malformations Library of Congress Catalog Card Number 72-86141 ISBN-13: 978-1-4684-3221-3 e-ISBN-13: 978-1-4684-3219-0 DOl: 10.1007/978-1-4684-3219-0 © 1972 Plenum Press, New York Softcover reprint of the hardcover 1st edition 1972 A Division of Plenum Publishing Corporation 227 West 17th Street, New York, N.Y. 10011 United Kingdom edition published by Plenum Press, London A Division of Plenum Publishing Company, Ltd. Davis House (4th Floor), 8 Scrubs Lane, Harlesden, London, NW10 6SE, England All rights reserved No part of this publication may he reproduced in any form without written permission from the publisher ORGANIZATION OF THE SYMPOSIUM Chairman of the Symposium: Prof. Marcus A. Klingberg Organizing Committee: Dr. A. Abramovici Prof. E.D. Bergmann Dr. J. Chemke Prof. S. Gitter Prof. I.G. Halbrecht Dr. M. Kesten - Treasurer Prof. M.A. Klingberg - Chairman Prof. S. Levin - Vice Chairman Prof. E. Liban - Vice Chairman Prof. H.N. Neufeld Prof. W.Z. Polishuk Prof. M. Streifler - Vice Chairman Dr. M. Torten - Secretary General vii Acknowledgement is gratefully made to the following firms who provided funds to help support the Symposium: ABIC LTD., Chemical & Pharmaceutical Industries, Ramat-Gan, Israel AGENTEX LTD., Tel-Aviv, Israel ASSIA CHEMICAL LABORATORIES LTD., Petah-Tikva, Israel lKAPHARM LTD., Pharmaceutical & Chemical Laboratories, Ramat-Gan, Israel NISSEN PREMINGER LTD., Medical Supplies, Tel-Aviv, Israel PHARMAPLANTEX LTD., Pharmaceutical Works, Nathanya, Israel RAFA LABORATORIES LTD., Jerusalem, Israel SANDOZ LTD., Basel, Switzerland TEVA MIDDLE EAST PHARMACEUTICAL & CHEMICAL WORKS LTD., Jerusalem, Israel VARON CHEMICALS LTD., Tel-Aviv, Israel viii FOREWORD This volume contains most of the papers presented at the First International Symposium on The Effect of Prolonged Drug Usage on Fetal Development held at the Beit-Berl Convention Center, Kfar Saba, Israel, on September 14 - 17, 1971. In order to obtain an overview of the effect of drugs on fetal development, it appeared desirable to gather the opinions of noted investigators regarding the goals already achieved and the future potential of prevention of fetal disorders due to drugs. More than one hundred and sixty scientists from fifteen countries participated, and over forty presented data which were collected in extensive laboratory, clinical and field studies. This small, comparatively informal, International Symposium was held in a relaxed environment and provided a suitable forum for scientists in many differing lines of research to evaluate together the recent advances in the role of drugs as teratogenic agents and methods for the rapid uncovering of the teratogenic potential of drugs to mankind. The success of the Symposium was due not only to the partici- pants who presented their papers, joined in the discussions, and so willingly cooperated in their contribution to this record of the conference, but in no small part to the efficient conduct of the Sessions by the Chairmen - Messrs. F. Bergmann, R.L. Brent, A.M. Davies, K.H. Degenhardt, S. Gitter, E. Liban, H. Lutz, U. Murakami, L. Nebel, H.N. Neufeld, W.Z. Polishuk, A. Robinson, J.A. Robson, L. Saxen, D.M. Serr, H.C. Shirkey, M. Streifler and J. Yerushalmy. We believe that this Symposium provided an opportunity for the cross fertilization and stimulation of ideas between scientists in the various disciplines. The present volume of the Proceedings shows how much has already been done and what prospects lie ahead. ix x FOREWORD The meeting could not have been organized without the help of of Dr. Michael Torten, Secretary of the Symposium, and Messrs. Mordechai Nawon and Menachem Iris who helped with extracurricular tasks. Likewise, we are happy to thank the secretaries, Mmes. Yehudity Lahav, Rachel Straks and Ilana Turner, for their tire- less efforts on our behalf. The editors wish to convey their warm appreciation to Mmes. Myra Kaye and LaVerne Binstock for their untiring help and effi- cient assistance in the editing and technical preparation of this book. This meeting was held thanks to the generous support of the Ministry of Health, Ministry of Tourism, Tel-Aviv University Medical School, the Israel Institute for Biological Research and the Israel Foundation Trustees, and of the ten pharmaceutical organizations already mentioned. Marcus A. Klingberg Armand Abramovici - Juan Chemke CONTENTS Chairman's Introductory Address ..... 3 Marcus A. Klingberg Congenital Malformations through the Ages 7 Josef Warkany Human Experiences Related to Adverse Drug Reactions to the Fetus or Neonate from Some Maternally Administered Drugs .. . . . . . 17 Harry C. Shirkey Drug Testing for Teratogenicity: Its Implications, Limitations and Application to Man. . .. 31 Robert L. Brent Sporadic Malformations in Laboratory Animals and Their Influence on Drug Testing . . . . . . 45 A. k. Palmer Fetal Outcome from Prolonged Versus Acute Drug Administration in the Pregnant Rat . . . . . 61' C. T. G. King, E. Horigan and A. L. wilk Multiphasic Screening, a Contribution to the Methodology of Teratological Research . 77 S. Sandor Study of Carbohydrate Metabolism in the Newborn Rat as a Tool for Evaluating Effects of Drugs Administered During Pregnancy . . . . . . . . . . . . . . . . . 8:) R. De Meyer, G. Verellen and P. Gerard Effects of Chemical Agents on Protein Biosynthesis During Embryonic Development . . . . 97 OWen M. Rennert Effect of Natural Teratogens in Poisonous Plants on Fetal Development in Domestic Animals ..... 107 Richard F. Keeler The Action of Different Pesticides on the Development of Bi rd Emb ryos . . . . . . . . . . . . 127 Hubert Lutz and Yvonne Lutz-Ostertag xi

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